Background: Worldwide estimates suggest that people living with HIV/AIDS (PLWH) smoke at nearly three times the rate of the general population. Smoking among PLWH living in sub-Saharan Africa is associated with gender (male>female), with living in an urban slum community, and perhaps most importantly with illicit substance use. Although precise prevalence estimates of tobacco use among PLWH in Kenya are lacking, recent data collected from a large, well established methadone maintenance program in Nairobi found the prevalence of smoking among PLWH with opiate use disorders was 100%. This compares to 7.7-9.1% in the Kenyan general population. Many interventions are effective in helping smokers in the general population quit. To what degree these data translate to PLWH in lower-middle income countries that may have greater challenges with health infrastructure, resources and medication access, is not clear. Approach: Our proposed study will use a factorial design to evaluate the most promising and accessible behavioral and pharmacologic treatments aimed at achieving maximal efficacy for smoking cessation among PLWH who smoke. We propose to randomize 300 participants PLWH, who smoke and who are receiving care in a methadone maintenance program in Nairobi, Kenya to one of the following 4 conditions: (1) bupropioin + Positively Smoke Free (an 8 session tailored behavioral intervention for PLWH smokers); (2) bupropion + Standard of Care (brief advice to quit); (3) Placebo + Positively Smoke Free; and (4) Placebo + Standard of Care. We plan to use a factorial design as it is a highly efficient method of assessing multiple treatments in a single trial with the possibility of saving both time and resources. We plan to conduct the study in a methadone maintenance clinic for several reasons. First, smoking rates are shockingly high in this setting, and the need for effective tobacco treatment is enormous. Second, there is great synergy in providing behavioral and pharmacological treatment for smoking cessation interventions to clients who are already receiving a pharmacological intervention (i.e., methadone) with concomitant substance use counseling. Third, people in methadone maintenance come regularly to receive treatment which is likely to enhance smoking cessation treatment follow-up and completion. All participants will be assessed at baseline,12 weeks and 36 weeks with the main outcome being 7-day abstinence (defined as self-reported no smoking in the past 7 days + CO<7 ppm). Additionally, we plan to conduct an implementation costs assessment to provide rigorously obtained approximations of total implementation costs of each intervention tested in this trial. Implications: As Kenya has one of the strongest anti-tobacco legislations in sub-Saharan Africa, results of this study will provide policymakers, community leaders and clinicians with critical evidence of the most effective smoking cessation treatments for PLWH smokers in the methadone maintenance setting.